Structure of 1423-26-3
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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
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| CAS No. : | 1423-26-3 |
| Formula : | C7H6BF3O2 |
| M.W : | 189.93 |
| SMILES Code : | FC(C1=CC(B(O)O)=CC=C1)(F)F |
| MDL No. : | MFCD00151854 |
| InChI Key : | WOAORAPRPVIATR-UHFFFAOYSA-N |
| Pubchem ID : | 2734388 |
| GHS Pictogram: |
|
| Signal Word: | Warning |
| Hazard Statements: | H315-H319-H335 |
| Precautionary Statements: | P261-P305+P351+P338 |
| Num. heavy atoms | 13 |
| Num. arom. heavy atoms | 6 |
| Fraction Csp3 | 0.14 |
| Num. rotatable bonds | 2 |
| Num. H-bond acceptors | 5.0 |
| Num. H-bond donors | 2.0 |
| Molar Refractivity | 41.27 |
| TPSA ? Topological Polar Surface Area: Calculated from |
40.46 Ų |
| Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
0.0 |
| Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.71 |
| Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.54 |
| Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.37 |
| Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
0.29 |
| Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.98 |
| Log S (ESOL):? ESOL: Topological method implemented from |
-2.3 |
| Solubility | 0.942 mg/ml ; 0.00496 mol/l |
| Class? Solubility class: Log S scale |
Soluble |
| Log S (Ali)? Ali: Topological method implemented from |
-2.18 |
| Solubility | 1.27 mg/ml ; 0.00668 mol/l |
| Class? Solubility class: Log S scale |
Soluble |
| Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.18 |
| Solubility | 1.26 mg/ml ; 0.00665 mol/l |
| Class? Solubility class: Log S scale |
Soluble |
| GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg |
High |
| BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg |
Yes |
| P-gp substrate? P-glycoprotein substrate: SVM model built on 1033 molecules (training set) |
No |
| CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) |
No |
| CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) |
No |
| CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) |
No |
| CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) |
No |
| CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) |
No |
| Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-6.24 cm/s |
| Lipinski? Lipinski (Pfizer) filter: implemented from |
0.0 |
| Ghose? Ghose filter: implemented from |
None |
| Veber? Veber (GSK) filter: implemented from |
0.0 |
| Egan? Egan (Pharmacia) filter: implemented from |
0.0 |
| Muegge? Muegge (Bayer) filter: implemented from |
1.0 |
| Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat |
0.55 |
| PAINS? Pan Assay Interference Structures: implemented from |
0.0 alert |
| Brenk? Structural Alert: implemented from |
1.0 alert: heavy_metal |
| Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW<1.0 |
| Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
1.72 |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

[ 29022-11-5 ]
[ 1423-26-3 ]
[ 210282-31-8 ]

[ 29022-11-5 ]
[ 1423-26-3 ]
[ 210282-31-8 ]

| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 47% | In toluene; at 20℃; for 2h; | The title compound (47%, oil) was prepared from 3-trifluoromethylphenylboronic acid and pinacol. 1H NMR (300 MHz, CDCl3): delta 1.35 (s, 12H), 7.48 (t, 1H), 7.70 (d, 1H), 7.97 (d, 1H), 8.06 (bs, 1H). |
[ 35265-82-8 ]
[ 1423-26-3 ]
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 89% | With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In water; toluene; for 2.0h;Heating / reflux; | To a toluene (10 mL)-water (1 mL) mixed solution of <strong>[35265-82-8]2,4-dichloro-6-methylthieno[3,2-d]pyrimidine</strong> (1.00 g, 4.56 mmol) were added 3-(trifluoromethyl)benzeneboronic acid (0.87 g, 4.56 mmol), sodium carbonate (0.97 g, 9.13 mmol), and tetrakis(triphenylphosphine)palladium (0.10 g, 5 mol%), followed by heating under reflux under a nitrogen stream for 2 hours. After completion of the reaction, the reaction liquid was poured into water and extracted with ethyl acetate. The resulting extract solution was washed with water and brine and then the solvent was removed by evaporation. The residue was purified on a silica gel column (Kiesel gel 60 manufactured by MERCK, 10% AcOEt-Hex) to obtain 2-chloro-6-methyl-4-[3-(trifluoromethyl)phenyl]thieno[3,2-d]pyrimidine (1.33 g, 89%). 1H-NMR (400MHz, CDCl3): 2.75(d, 3H, J=1.2Hz), 7.26(d, 1H, J=1.2Hz), 7.72(t, 1H, J=8.0Hz), 7.85(d, 1H, J=8.0Hz), 8.36(d, 1H, J=8.0Hz), 8.43(s, 1H). mp: 174-176C (dec.) |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In toluene; for 10h;Heating / reflux;Product distribution / selectivity; | Example 11: 4-(3,3,4-Trimethyl-4-oxy-piperazin-1-yl)-6-(3-trifluoromethyl-phenyl)- pyrimidine-2-carbonitrile A: 2-Methylsulfanyl-6-(3-trifluoromethylphenyl)-pyrimidin-4-ylamine To a stirred solution of <strong>[1005-38-5]4-amino-6-chloro-2-methylthiopyrimidine</strong> (3.5 g) in toluene (45 ml.) under a nitrogen atmosphere was added, sequentially, 3-(trifluoro- methyl)phenylboronic acid (4.15 g), potassium carbonate (25 ml_, 2M) and tetrakis- (triphenylphosphine)palladium(O) (1.16 g). The mixture was heated to reflux for ten hours. Ethyl acetate (15OmL) was added and the mixture washed with water (2 x 100 ml_). Organic layer was separated, washed with saturated sodium chloride (100 ml_), dried over sodium sulphate and solvent was evaporated under reduced pressure to yield crude product. Purification by flash chromatography yielded product 2-methyl- sulfanyl-6-(3-trifluoromethyl-phenyl)-pyrimidin-4-ylamine (3.45 g) 1H NMR (CDCI3): delta 8.25 (s, 1 H), 8.19 (d, 1 H), 7.70 (d, 1 H), 7.58 (t, 1 H), 6.56 (s, 1 H), 4.92 (s, 2H), 2.61 (s, 3H). MS m/z: 286.3 (M+1 ). | |
| With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In water; toluene; at 20℃;Heating / reflux;Product distribution / selectivity; | To a stirred solution of <strong>[1005-38-5]4-amino-6-chloro-2-methylthiopyrimidine</strong> (3.5 g) in toluene (45 mL) under a nitrogen atmosphere was added, sequentially, 3-(trifluoromethyl)phenylboronic acid (4.15 g), potassium carbonate (25 mL, 2M) and tetrakis(triphenylphosphine)palladium(0) (1.16 g). The mixture was heated to reflux for ten hours. Ethyl acetate (150 mL) was added and the mixture washed with water (2.x.100 mL). Organic layer was separated, washed with saturated sodium chloride (100 mL), dried over sodium sulphate and solvent was evaporated under reduced pressure to yield crude product. Purification by flash chromatography yielded product 2-methylsulfanyl-6-(3-trifluoromethyl-phenyl)-pyrimidin-4-ylamine (3.45 g) 1H NMR (CDCl3): delta 8.25 (s, 1H), 8.19 (d, 1H), 7.70 (d, 1H), 7.58 (t, 1H), 6.56 (s, 1H), 4.92 (s, 2H), 2.61 (s, 3H). MS m/z: 286.3 (M+1).; A: 2-Methylsulfanyl-6-(3-trifluoromethylphenyl)-pyrimidin-4-ylamine To a stirred solution of <strong>[1005-38-5]4-amino-6-chloro-2-methylthiopyrimidine</strong> (3.5 g) in toluene (45 mL) under a nitrogen atmosphere was added, sequentially, (3-trifluoromethylphenyl)boronic acid (4.15 g), potassium carbonate (25 mL, 2M) and tetrakis(triphenylphosphine)palladium(0) (1.16 g). The mixture was heated to reflux for ten hours and stirred at room temperature over the weekend. Ethyl acetate (150 mL) was added and the mixture washed with water (2.x.100 mL). Organics were separated, washed with saturated sodium chloride (100 mL), dried over sodium sulphate and solvent was evaporated under reduced pressure to yield crude product. Purification by flash chromatography yielded product 2-methylsulfanyl-6-(3-trifluoromethyl-phenyl)-pyrimidin-4-ylamine (3.45 g) 1H NMR (CDCl3): 8.25 (s, 1H), 8.19 (d, 1H), 7.70 (d, 1H), 7.58 (t, 1H), 6.56 (s, 1H), 4.92 (s, 2H), 2.61 (s, 3H). MS m/z 286.3 (M+1). |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| With caesium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; water; at 50℃; | 6-bromo-3,4-dihydro-2H-pyrido[3,2-b] [l ,4]oxazine (5; 2.0 g, 9.30 mmol), 3-(trifluromethyl)- phenylboronic acid (2.65 g, 1 3.95 mmol), Pd(Ph3)4 (21 5 mg, 0. 186 mmol) and CsCO3 (6.0 g, 18.6 mmol) were all dissolved in dioxane:H20 mixture (45 mL: l mL) and heated to 50 C overnight. Product peak seen by LCMS, but some starting material remained, added more boronic acid and stirred at 50 C overnight. The starting material peak was unchanged, cooled to room temp and some precipitates started to crash out. Diluted with water (40 mL), extracted with EtOAc (3 x 40 mL), washed with brine, dried over MgS04, filtered, concentrated and purified through I SCO silica column (0 to 100% EtOAc/pentanes) to collect mixed fractions of 6-(3-(trifluoromethyl)phenyl)-3,4-dihydro-2H-pyrido[3,2-b][ l ,4]oxazine (6) M S (ESI) calcd for C 14H1 1 F3N2O (m/z) 280.08, found 281 [M+H]. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 52% | With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; water; at 120℃; for 12h;Inert atmosphere; sealed tube; | 2-Chloro-7,8-dihydro-6H-pyrimido[5,4-b][l,4]oxazine (68; 1.41 g, 8.22 mmol), 3- (trifluoromethyl)phenylboronic acid (1.87 g, 9.86 mmol), Pd(PPh3)4 (475 mg, 0.411 mmol), Na2C03 (2.09 g, 19.7 mmol) and dioxane/water(4:l, 35 ml) were added to a sealed tube and filled with nitrogen. Then the mixture was heated to 120 C for 12 hours. After cooling, CH2CI2 (100 mL) was added and the mixture was passed through a pad of Na2SO |
[ 52133-67-2 ]
[ 1423-26-3 ]
[ 120157-97-3 ]
[ 1423-26-3 ]
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 56% | General procedure: A mixture of N-boc-2-(4-bromophenyl)ethylamine, the desiredarylboronic acid (a-m) (1.2 equiv), tetrakis(triphenylphosphine)-palladium(0) (0.04 equiv), Na2CO3 (5 equiv) in degassed toluene/H2O (5/2) was refluxed for 18 h. The reaction mixture was filteredthrough Celite and concentrated in vacuo. The resulting residuewas dissolved in in EtOAc (200 mL), washed with H2O (200 mL 2) and brine (200 mL). The organic layer was dried with anhydrousNa2SO4 and concentrated in vacuo. The residue was purified by columnchromatography on SiO2.Using Method E, 13 (1.00?g, 3.3?mmol), 3-(trifluoromethyl)phenylboronic acid (0.76?g, 4.0?mmol), tetrakis(triphenylphosphine)palladium(0) (0.15?g, 0.1?mmol), Na2CO3 (1.77?g, 16.7?mmol) in toluene/H2O (33?ml/13.3?ml), followed by 4.0?M HCl in dioxane (2.50?ml, 10.0?mmol) gave 14a as a white solid (0.57?g, 56%): Rf?=?0.00 (EtOAc 9: acetone 1): 1H NMR (DMSO-d6, 400?MHz) delta 2.98-3.10 (m, NH3CH2CH2), 7.42 (d, J?=?8.2?Hz, 2 ArH), 7.69-7.74 (m, 4 ArH), 7.95-8.00 (m, 2 ArH), 8.31 (s, NH3); 13C NMR (DMSO-d6, 100?MHz) delta 33.0 (NCH2CH2), 123.4 (q, JC-F?=?3.9?Hz), 124.4 (q, JC-F?=?3.7?Hz), 124.7 (CF3, q, JC-F?=?270.9?Hz), 127.6, 129.9, 130.2 (q, JC-F?=?31.4?Hz), 130.5, 131.1, 137.4, 138.1, 141.4 (12 ArC). |

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